The object of the experiment is to determine the amount of variation of structural genes coding for enzymes and other proteins in natural populations, and to correctly identify the forces determining this variation. This problem is attacked chiefly at the level of DNA sequence variation for both polymorphic and monomorphic genes in Drosophila. The purpose of choosing DNA sequence to study protein variation is two-fold. First, it is the only practicable method for obtaining complete information on all the amino acid substitution variation carried in natural populations. Second, because of the differentiation of genes into introns, exons, flanking sequences, non-silent and silent sites, it is possible to discern the forces of selection and genetic drift by comparing polymorphism of amino acid with silent sites and introns. We will study DNA variation in polymorphic genes like Esterase-5 and in D. pseudoobscura and monomorphic genes such as chorion genes, heat shock genes and glycerol-3-phosphate dehydrogenase. The kinds of genetic variation in enzyme molecules present in populations, and the forces of selection operating on them is of direct interest to problems of genetic diseases and to variation in reactions to drugs and environmental stress.